Objective. To verify the association of ribosomal anti‐P antibodies (anti‐P), as detected by a sensitive ELISA, with serological findings and clinical manifestations, including neuropsychiatric involvement evaluated according to the American College of Rheumatology (ACR) nomenclature, in a large cohort of patients with systemic lupus erythematosus (SLE). Methods. Anti‐P were evaluated in the serum of 149 consecutive Italian SLE patients by an ELISA using a multiple antigen peptide carrying four copies of a common P0, P1 and P2 epitope. A complete laboratory evaluation and clinical examination were performed in each patient. In addition, all patients underwent an accurate neuropsychiatric and neuropsychological assessment performed by trained specialists according to the 1999 ACR suggestions. Results. Serum anti‐P were detected in 18/149 patients (12.1%). The anti‐P prevalence was similar (11.7%) when the analysis was performed in a larger series of sera including 82 additional SLE patients, who were not included in the clinical study. The age of anti‐P‐positive patients at disease onset was less than 33 yr and, in comparison with the anti‐P‐negative patients, these patients showed more active disease activity and a higher prevalence of photosensitivity and malar and discoid rash. A strong association between IgG anticardiolipin antibodies and anti‐P was also found. However, anti‐P were associated with neither neuropsychiatric syndromes nor cognitive impairment. Conclusion. This study does not seem to confirm the described association of anti‐P with SLE neuropsychiatric manifestations. However, it supports the anti‐P association with different skin manifestations as well as the presence of anticardiolipin in a subset of patients with SLE characterized by early disease onset.

Background: Autoantibodies to citrullinated proteins (ACPA) are considered a specific marker for rheumatoid arthritis. Peptidylarginine deiminase (PAD) is the enzyme that converts arginyl into citrullyl residues; different isoforms of the enzyme are expressed in mammals. It has been suggested that the PADI4 gene may contribute to genetic susceptibility to rheumatoid arthritis, but conflicting results have been obtained in different populations. Objective: To test the hypothesis that the PADI4 gene may confer susceptibility to rheumatoid arthritis in a white French population, using powerful and highly reliable family based association tests. Methods: DNA samples were analysed from 100 families where one member was affected by rheumatoid arthritis and both parents were available for sampling. Five single nucleotide polymorphisms, located within the PADI4 gene and in its close proximity, were genotyped by restriction fragment length polymorphism, and haplotypes were constructed. The analysis involved use of the transmission disequilibrium test and genotype relative risk. ACPA were detected by ELISA on cyclic citrullinated peptides and on human deiminated fibrinogen. Results: No single SNP or haplotype was associated with the disease, or was preferentially transmitted. No association was found when patients were partitioned according to ACPA positivity. Conclusions: No PADI4 haplotype is associated with rheumatoid arthritis in a white French population. The role of genes encoding the other PAD isoforms, or modulating tissue expression or enzyme activity, remains to be elucidated.

Transthyretin (TTR) is a homotetrameric protein mainly synthesised by the liver and the choroid plexus whose function is to carry the thyroid hormone thyroxine and the retinol-binding protein bound to retinol in plasma and cerebrospinal fluid. When the stability of the tetrameric structure is lost, it breaks down, paving the way for the aggregation of TTR monomers into insoluble fibrils leading to transthyretin (ATTR) amyloidosis, a progressive disorder mainly affecting the heart and nervous system. Several TTR gene mutations have been characterised as destabilisers of TTR structure and are associated with hereditary forms of ATTR amyloidosis. The reason why also the wild-type TTR is intrinsically amyloidogenic in some subjects is largely unknown. The aim of the review is to give an overview of the TTR biological life cycle which is largely unknown. For this purpose, the current knowledge on TTR physiological metabolism, from its synthesis to its catabolism, is described. Furthermore, a large section of the review is dedicated to examining in depth the role of mutations and physiological ligands on the stability of TTR tetramers.

Anti-ribosomal P protein antibodies (Abs) recognize three specific ribosomal proteins located in the large ribosome's subunit. The term anti-ribosomal P protein Abs, often shortened in anti-P Abs, is due to the fact that these three proteins, P0, P1 and P2, of 38, 19 and 17 Kd molecular weight, respectively, are phosphorylated. One of the major points of interest of these autoAbs derives from their high specificity for systemic lupus erythematosus (SLE), their description in other connective tissue diseases (CTDs) being only occasional. In SLE patients, their association with renal and hepatic involvement has been proposed, while the possible association with psychiatric and/or neurological involvement is still a matter of debate. From a serological point of view, a preferential association of anti-P with anti-Sm and/or anti-DNA Abs, possibly due, at least in part, to cross-reactivity, has been suggested. This observation is intriguing since all these autoAbs are considered specific serological indicators of SLE. This review will summarize clinical and serological data on anti-P Abs provided by the main studies published in the last few years and the more recent findings about proteins constituting their targets.